Spark’s de­liv­ery vec­tor trig­gers an­oth­er trou­bling im­mune re­ac­tion, but R&D team main­tains he­mo­phil­ia B ef­fi­ca­cy

Kather­ine A. High, Spark

One month af­ter Spark Ther­a­peu­tics $ONCE spooked its in­vestors with the news of one im­mune re­ac­tion to its gene ther­a­py in a small he­mo­phil­ia B study, its in­ves­ti­ga­tors turned up at ASH to add one more case to con­cern its back­ers. But the biotech wasn’t un­pre­pared, com­ing back with ev­i­dence that they were still able to con­trol the im­mune re­ac­tion to SPK-9001 while all but one of 9 pa­tients clear­ly re­mained free of bleeds.

An im­mune re­ac­tion is one thing you nev­er want to see af­ter de­liv­er­ing a gene ther­a­py, which us­es in­ac­ti­vat­ed virus­es to try and safe­ly de­liv­er a gene fix for a par­tic­u­lar ge­net­ic mal­func­tion. But the spike in liv­er en­zymes flagged an im­mune re­sponse to the Spark100 de­liv­ery ve­hi­cle for two pa­tients. Fac­tor IX ac­tiv­i­ty — the pro­tein need­ed for blood to clot — dropped from 32% to 12% in one of those pa­tients, but stayed at a ther­a­peu­tic lev­el.

Re­searchers put that pa­tient on a ta­per­ing course of cor­ti­cos­teroids. The oth­er im­mune re­sponse was dealt with more quick­ly with steroids, and the Fac­tor IX peak ac­tiv­i­ty slipped from 71% to 68%.

One of the 9 need­ed an in­fu­sion to con­trol a sus­pect­ed knee bleed even though the par­tic­i­pant has a Fac­tor IX lev­el of 36%.

This time around Spark, which is part­nered with phar­ma gi­ant Pfiz­er $PFE, was ready to start re­as­sur­ing ob­servers, even though it had more bad news to de­liv­er.

“We will mon­i­tor these two par­tic­i­pants care­ful­ly as we con­tin­ue to ta­per the cor­ti­cos­teroids,” said Kather­ine A. High, M.D., pres­i­dent and chief sci­en­tif­ic of­fi­cer at Spark Ther­a­peu­tics, in a state­ment. “It’s im­por­tant to re­mem­ber that the im­mune re­sponse to the cap­sid typ­i­cal­ly is tran­sient, and in both cas­es, seems to have been ar­rest­ed by cor­ti­cos­teroids. Once cor­ti­cos­teroids have been dis­con­tin­ued al­to­geth­er, lev­els of ex­pres­sion will be the best mea­sure of the ef­fi­ca­cy of this ap­proach. The ex­pe­ri­ence we have gained in im­muno-mon­i­tor­ing and in clin­i­cal man­age­ment of the im­mune re­sponse in the he­mo­phil­ia B tri­al will fur­ther in­form our up­com­ing he­mo­phil­ia stud­ies.”

It’s fi­nal­ly over: Bio­gen, Ei­sai scrap big Alzheimer’s PhI­I­Is af­ter a pre­dictable BACE cat­a­stro­phe rais­es safe­ty fears

Months after analysts and investors called on Biogen and Eisai to scrap their BACE drug for Alzheimer’s and move on in the wake of a string of late-stage failures and rising safety fears, the partners have called it quits. And they said they were dropping the drug — elenbecestat — after the independent monitoring board raised concerns about…safety.

We don’t know exactly what researchers found in this latest catastrophe, but the companies noted in their release that investigators had determined that the drug was flunking the risk/benefit analysis.

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Lisa M. DeAngelis, MSKCC

MSK picks brain can­cer ex­pert Lisa DeAn­ge­lis as its next CMO — fol­low­ing José Basel­ga’s con­tro­ver­sial ex­it

It’s official. Memorial Sloan Kettering has picked a brain cancer expert as its new physician-in-chief and CMO, replacing José Baselga, who left under a cloud after being singled out by The New York Times and ProPublica for failing to properly air his lucrative industry ties.

His replacement, who now will be in charge of MSK’s cutting-edge research work as well as the cancer care delivered by hundreds of practitioners, is Lisa M. DeAngelis. DeAngelis had been chair of the neurology department and co-founder of MSK’s brain tumor center and was moved in to the acting CMO role in the wake of Baselga’s departure.

Penn team adapts CAR-T tech, reengi­neer­ing mouse cells to treat car­diac fi­bro­sis

After establishing itself as one of the pioneer research centers in the world for CAR-T cancer therapies, creating new attack vehicles to eradicate cancer cells, a team at Penn Medicine has begun the tricky transition of using the basic technology for heart repair work.

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Tal Zaks. Moderna

The mR­NA uni­corn Mod­er­na has more ear­ly-stage hu­man da­ta it wants to show off — reach­ing new peaks in prov­ing the po­ten­tial

The whole messenger RNA field has attracted billions of dollars in public and private investor cash gambled on the prospect of getting in on the ground floor. And this morning Boston-based Moderna, one of the leaders in the field, wants to show off a few more of the cards it has to play to prove to you that they’re really in the game.

The whole hand, of course, has yet to be dealt. And there’s no telling who gets to walk with a share of the pot. But any cards on display at this point — especially after being accused of keeping its deck under lock and key — will attract plenty of attention from some very wary, and wired, observers.

“In terms of the complexity and unmet need,” says Tal Zaks, the chief medical officer, “this is peak for what we’ve accomplished.”

Moderna has two Phase I studies it wants to talk about now.

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It's not per­fect, but it's a good start: FDA pan­elists large­ly en­dorse Aim­mune's peanut al­ler­gy ther­a­py

Two days after a fairly benign review from FDA staff, an independent panel of experts largely endorsed the efficacy and safety of Aimmune’s peanut allergy therapy, laying the groundwork for approval with a risk evaluation and mitigation strategy (REMS).

Traditionally, peanut allergies are managed by avoidance, but the threat of accidental exposure cannot be nullified. Some allergists have devised a way to dose patients off-label with peanut protein derived from supermarket products to wean them off their allergies. But the idea behind Aimmune’s product was to standardize the peanut protein, and track the process of desensitization — so when accidental exposure in the real world invariably occurs, patients are less likely to experience a life-threatening allergic reaction.

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Rit­ter bombs fi­nal PhI­II for sole lac­tose in­tol­er­ance drug — shares plum­met

More than two years ago Ritter Pharmaceuticals managed to find enough silver lining in its Phase IIb/III study — after missing the top-line mark — to propel its lactose intolerance toward a confirmatory trial. But as it turned out, the enthusiasm only set the biotech and its investors up to be sorely disappointed.

This time around there’s little left to salvage. Not only did RP-G28 fail to beat placebo in reducing lactose intolerance symptoms, patients in the treatment group actually averaged a smaller improvement. On a composite score measuring symptoms like abdominal pain, cramping, bloating and gas, patients given the drug had a mean reduction of 3.159 while the placebo cohort saw a 3.420 drop on average (one-sided p-value = 0.0106).

Ear­ly snap­shot of Ad­verum's eye gene ther­a­py sparks con­cern about vi­sion loss

An early-stage update on Adverum Biotechnologies’ intravitreal gene therapy has triggered investor concern, after patients with wet age-related macular degeneration (AMD) saw their vision deteriorate, despite signs that the treatment is improving retinal anatomy.

Adverum, on Wednesday, unveiled 24-week data from the OPTIC trial of its experimental therapy, ADVM-022, in six patients who have been administered with one dose of the therapy. On average, patients in the trial had severe disease with an average of 6.2 anti-VEGF injections in the eight months prior to screening and an average annualized injection frequency of 9.3 injections.

Alex Ar­faei trades his an­a­lyst's post for a new role as biotech VC; Sanofi vet heads to Vi­for

Too often, Alex Arfaei arrived too late. 

An analyst at BMO Capital Markets, he’d meet with biotech or pharmaceutical heads for their IPO or secondary funding and his brain, trained on a biology degree and six years at Merck and Endo, would spring with questions: Why this biomarker? Why this design? Why not this endpoint? Not that he could do anything about it. These execs were coming for clinical money; their decisions had been made and finalized long ago.

Arde­lyx bags its first FDA OK for IBS, set­ting up a show­down with Al­ler­gan, Iron­wood

In the first of what it hopes will be a couple of major regulatory milestones for its new drug, Ardelyx has bagged an FDA approval to market Ibsrela (tenapanor) for irritable bowel syndrome.

The drug’s first application will be for IBS with constipation (IBS-C), inhibiting sodium-hydrogen exchanger NHE3 in the GI tract in such a way as to increase bowel movements and decrease abdominal pain. This comes on the heels of two successful Phase III trials.